Not all senior dogs develop cognitive deterioration and in most they are mild but some pets do develop overt cognitive dysfunction syndrome. Owners of affected pets often find it increasingly difficult to cope with the changes in their pets’ behaviour and the human-animal bond can be stressed or broken. Many owners will need to make painful decisions based upon both their own and their pets’ quality of life.

A study showed that 28% of owners of dogs 10 – 11 years old report at least one sign of cognitive change but this increases to 68% of owners of 15 – 16 year old dogs. In pets which are trained – such as guide dogs and working dogs – dysfunction may detected at an earlier age. The most commonly reported signs of cognitive dysfunction in dogs is aimless pacing and wandering and staring blankly (91%) and avoiding being patted and difficulty finding dropped food (75%).

The typical age of onset of presentation of cognitive decline in pets is traditionally set at about 11 years of age, based on owner reports. When data from laboratory animals studied with standardised assessment tools are evaluated however, the decline is noted to start at about seven years of age. This discrepancy emphasises the insidious nature of the change.

Owners do not usually present their animals to their veterinarian vet for cognitive dysfunction as they assume the changes are just unavoidable ageing. It is thus imperative that veterinarians are proactive in asking questions regarding changes in behaviour during a consultation and also in educating their clients in this condition. In a marketing study by Hills Pet Nutrition, 75% of owners of dogs aged 7 years and older reported at least one change in behaviour consistent with cognitive dysfunction but only 12% of these owners had reported the change to their veterinarian of their own accord.

Brain Function and Ageing

With increasing age there is a reduction in brain mass, increased ventricular size, meningeal calcification, demyelination and glial changes, neuro-axonal degeneration and a reduction in neurons. In dogs, cats and human beings with cognitive dysfunction there is also an increased accumulation of diffuse beta -amyloid plaques and perivascular infiltrates. In humans neurofibrillar tangle formation is an important component of the disease. This is not seen in dogs but is seen in cats. Cerebral arteriorsclerosis may also be seen in older dogs and cats resulting in compromised blood flow. Changes are irreversible but clinical signs can be managed and improved.

The brain is highly metabolically active, accounting for 2-3% of body weight yet consuming 25% of available glucose. Normally glucose is the main energy source of the brain. Cerebral glucose metabolism is reduced in healthy ageing people and dogs. Cerebral glucose metabolism correlates strongly with cognitive function and reduced metabolism occurs years before clinical signs are evident.

With ageing there is an increase in reactive oxygen species leading to oxidative damage. The brain may be particularly susceptible of the effects of free radicals because of its high lipid content, high rate of oxidative metabolism and limited ability for regeneration. Functional changes in the ageing brain include depletion of monoamine oxidase inhibitors (MAOIs) and a decline in cholinergic activity. Increases in MAO activity increases dopamine catabolism and also increases free radicals. Widespread oxidative damages , free radical production and lowered Vitamin E levels have all been demonstrated in dogs with dementia

Ketone bodies (KB) can be used as an alternative energy source for the brain when available;–prolonged starvation, and high fat- low carbohydrate diets. KB can supply up to 60% of the energy requirements of the brain during starvation in humans.

Collectively these ageing changes cause working memory dysfunction as well as alterations in motor function and REM sleep.

CLINICAL PRESENTATION

The most central diagnostic tool for detecting CCD is owner-based (Tables 1 and 2).

Many of the behavioural complaints of older pets are related to anxiety, including an increased prevalence of separation anxiety, phobias, excessive vocalisation, aggression and waking at nights. Not all such changes in the older dog are due to cognitive dysfunction . Other disease process which may cause or contribute to these signs must be excluded.(Table 3)

Because neurophsychological testing procedures of dogs and cats are now standardised therapeutic interventions can now also be evaluated and in some cases, approved, for use in clinical cases. Drugs, dietary changes and environmental enrichment and adjustment are the three mainstays of treatment.

Drugs: (See table 4)

Drug Doses for Behaviour Therapy

Dog

Cat

Alprazolam

0.02 -0.1 mg/kg bid -qid

0.125-.025mg/cat oid – tid

Diazepam

0.5 – 2 mg oid – qid

0.2 -0.5mg/kg bid – tid

Oxazepam

0.2 – 1mg oid – bid

0.2 – 0.5 mg/kg oid – bid

Clonazepam

0.1 – 1.0 mg/kg bid – tid

0.02 – 0.2 mg/kg oid – bid

Lorazepam

0.025 – 0.2mg/kg oid – tid

0.025 – 0.05 mg/kg oid – bid

Melatonin

3-9 mg/dog

1.5 – 6 mg/cat

Diphenhydramine

2-4 mg /kg

1-4 mg/kg

Fluoxetine

1.0 – 2.0 mg/kg oid

0.5 – 1 mg/kg oid

Sertraline

1-5 mg/kg oid or 2.5 mg/kg bid

0.5 – 1.5 mg/kg oid

Buspirone

0.5 – 2.0 oid – tid

0.5 – 1 mg bid

Trazadone

2 – 5mg/kg as needed up to 8 – 10mgmg bid – tid

Not determined

Phenobarbital

2.5 – 5mg/kg bid

2.5 mg/kg bid

Gabapentin

10 – 30 mg /kg bid -tid

5 – 10mg/kg oid -tid

Potassium bromide

10 – 35 mg/kg daily or in divided doses

Not recommended

Selegiline

0.5 – 1 mg/kg oid in the am

0.5 – 1 mg/kg oid in am

Memantine

0.3 – 1 mg/kg oid

Not determined

Amantadine

1.25 – 4 mg/kg per os oid -bid

3mg/kg per os oid

Selegiline

Selegiline is a selective irreversible monoamine oxidase B inhibitor (MAOB). The mechanism by which it causes its effect in dogs is not clear but three concurrent actions are proposed:

increases 2-phenyl ethylamine (PEA) in the dog brain, a neuromodulater which enhances dopamine and catecholamine function and itself enhances congnitive function. Catecholamine enhancements may lead to enhance neuronal transmission. S

contributes to decreasing the free radical load in the brain by scavenging free radicals and enhancing scavenging enzymes such as superoxide dismutase (SOD) and catalase.

is neuroprotective effect on dopaminergic, noradrenergic and adrenergic neurons

Dose: 0.5 – 1 mg /kg oid in am. If there is not significant improvement in 30 days the dose can be adjusted upwards for another month. Toxicity can occur if used concurrently with other MOAIs.

Drugs for enhancing cerebral perfusion

Propentophylline (KarsivanÒ) is licensed for the treatment of dullness and lethargy in older dogs

Drugs enhancing the noradrenergic system:

Nicergoline : alpha 1 and alpha 2 adrenergic antagonist.

Adrafanil, modafinil: enhance noradrenergic system –improve alertness and help maintain normal sleep-wake cycle by increasing daytime exploration and activity. The noradrenergic system helps to maintain alertness, wakefulness, attention, memory and learning and also functions in neuroprotection. Treatment with these drugs causes improved learning but long term decreased memory – highlighting the need to test the full cognitive range when evaluating an intervention.

Anxiolytics and antidepressants:

Alterations in neurotransmission can lead to irritability, decreased responsiveness to stimuli, fear, and agitation. Antidepressants and anxiolytics may be considered in some older pets. These include clomipramine , amitriptyline, fluoxetine, and paroxetine benzodiazepines and buspirone.

Cholinergic function in the brain is important for memory and older dogs show a greater sensitivity to cholinergic disruption which impairs working memory. Clomipramine, paroxetine and amitryptiline are anticholinergic and should be used with care – drugs selected should also enhance and not reduce neuronal cholinergic activity if possible.

DIET

Dietary strategies involve supplementation with anti-oxidants and mitochondrial co-factors to improve anti-oxidant defences as well as reduce production and toxic effects of, and increase clearance of, oxygen free radicals. Vitamins E and C, beta-carotene, selenium, and other flavonoids and carotenoids from fruits and vegetables have antioxidant and anti-inflammatory properties in the treatment of cognitive dysfunction. B vitamins (thiamine, riboflavin, niacin b6 and B12)may also have antioxidant and neuroprotective effects as well as the ability to normalise neurotransmitter levels. Enhancement of mitochondrial function is achieved with the addition of L-carnitine and DL-alpha-lipoic acid.

The efficacy of Hills B/D has been evaluated over a trial period of 2 years using neurophsychological testing well as in clinical trials and was found to improve performance on a number of cognitive tasks beginning as early as 2-8 weeks after onset of the diet. In a 60 day double blinded clinical trial of 142 dogs there was a significantly greater improvement in cognitive function in the treated group than in the control group.

Traditional ketogenic diets are high in fat low in protein and very low in carbohydrates, this is unsuitable for old dogs due to protein catabolism and muscle wasting which normally occurs in ageing. Dietary medium chain triglyceride (MCT) supplementation can increase blood ketone body levels without restricting dietary proteins and carbohydrates. This increased supply of an alternative energy source can improve cognitive performance. A diet containing MCT (Purina One Vibrant Maturity 7+ for dogs)has been shown to improve cognitive function.

Instead of only focusing on the treatment of clinical signs more effort should be made to utilise the many products containing antioxidant and neuroprotective substances to slow the progression of the disease by starting treatment at an earlier age, even before owners detect cognistive impairment as laboratory test have shown impairment starts insidiously from about 7 years of age.

Environmental enrichment

Dogs without environmental enrichment show a more rapid decline in cognitive function. The dogs in the groups with dietary supplementation (Hills B/D) or environmental enrichment did better than those control animals without dietary or environmental improvements. The greatest effect was seen with combined dietary supplementation and environmental enrichment.

Practical tips: Food puzzle toys, interactive toys, play and exercise and training, night light as vision deteriorates, help maintain temporal orientation with odours (scented candles), tactile (flooring) and auditory cues to help. Pherormone therapy as an anxiolytic (FeliwayÒ). Keep up a predictable routine to reduce anxiety, and keep the dog active during the day so that it sleeps at night. Training , play exercise and novelty toys.

CATS:

Cognitive dysfunction in cats is not as clearly researched as in dogs. Old age in cats is accompanied by altered behaviour such as wandering, vocalisation and night time activity , which are not attribuible to medical problems. These changes can start from about 10 years of age with a significant increase in older cats. Cats are more likely to present with excessive vocalisation and night time activity. Several supplements for senior cats are available in Europe : Cholodin-Fel (MVP Labs) , Senilife (CEVA Animal Health), Activaite (VetPlus).